Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Bo Gao, Amanda Russell, Jonathan Beesley, Xiaoqing Chen, Sue Healey, Michelle Henderson, Mark Wong, Catherine Emmanuel, Laura Galletta, Sharon Johnatty, David Bowtell, Michelle Haber, Murray Norris, Paul Harnett, G Chenevix-Trench, Rosemary Balleine, Anna DeFazio, Dorota Gertig, Adele Green, Penelope WebbJillian Hung, Sue Moore, Nadia Traficante, Sian Fereday, Karen Harrap, Troy Sadkowsky, Nirmala Pandeya, Robin Stuart-Harris, Fred Kirsten, Josie Rutovitz, Peter Clingan, Amanda Glasgow, Anthony Proietto, Stephen Braye, Greg Otton, J Shannon, Tony Bonaventura, Stewart James, Stephen Begbie, Michael Friedlander, David Bell, Sally Baron-Hay, Alan Ferrier, Gregory Gard, David Nevell, Nick Pavlakis, Sue Valmadre, Barbara Young, Catherine Camaris, Roger Crouch, Lyndal Edwards, Neville Hacker, Donald Marsden, Greg Robertson, Philip Beale, Jane Beith, Jonothan Carter, Chris Dalrymple, Anne Hamilton, Roger Houghton, Peter Russell, Matthew Links, John Grygiel, Jane Hill, Alison Brand, K Byth, Richard Jaworski, Raghwa Sharma, Anita Achen, Gerard Wain, Bruce Ward, David Papadimos, Alex Crandon, Margaret Cummings, Ken Horwood, Andreas Obermair, Lew Perrin, David Wyld, James Nicklin, Margaret Davy, Martin Oehler, Christina Hall, Thomas Dodd, Tabitha Healy, Ken Pittman, Douglas Henderson, John Miller, John Pierdes, Penny Blomfield, David Challis, Robert McIntosh, Andrew Parker, Bob Brown, Robert Rome, David Allen, Peter Grant, Simon Hyde, Rohan Laurie, Melissa Robbie, David Healy, Thomas Jobling, Thomas Manolitsas, Jane McNealage, Peter Rogers, Beatrice Susil, Eric Sumithran, Ian Simpson, Kelly Phillips, Danny Rischin, Stephen Fox, Daryl Johnson, Paul Waring, Stephen Lade, Maurice Loughrey, Neil O'Callaghan, William Murray, Virginia Billson, Jan Pyman, Debra Neesham, Michael Quinn, Craig Underhill, Richard Bell, Leong Ng, R Blum, Vinod Ganju, Ian Hammond, Yee Leung, Anthony McCartney, Martin Buck, Izak Haviv, David Purdie, David Whiteman, Nikolajs Zeps, Mary Malt, Anne Mellon, Randall Robertson, Trish Vanden Bergh, Marian Jones, Patricia Mackenzie, Jane Maidens, Kathryn Nattress, Yoke Chiew, Annie Stenlake, Helen Sullivan, Barbara Alexander, Pat Ashover, Sue Brown, Tracy Corrish, Lyn Green, Lea Jackman, Kaltin Ferguson, Karen Martin, Adam Martyn, Barbara Ranieri, Joanne White, Victoria Jayde, Leanne Bowes, Pamela Mamers, Debra Giles, Joy Hendley, Allsopp Katherine, Trudy Schmidt, Helen Shirley, Colleen Ball, Cherry Young, Suzanna Viduka, Hoa Tran, Sanela Bilic, Lydia Galvinas, Julia Brooks

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.

    Original languageEnglish
    Article number4669
    Number of pages9
    JournalScientific Reports
    Volume4
    Issue number4669
    DOIs
    Publication statusPublished - 2014

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